Effect and mechanism of mogrol on lipopolysaccharide-induced acute lung injury / 中华急诊医学杂志

ABSTRACT

Objective:To explore the targeted regulation of the inflammatory pathway and its mechanism after AMPK phosphorylation induced by lipopolysaccharide (LPS) in mice and human monocytes induced by THP-1, so as to provide evidence for the clinical application of Mogrol (MO) in the clinical treatment of acute lung injury.Methods:Twenty-four clean C57BL/6 male mice aged 6-8 weeks were randomly (random number) divided into the control group, MO group, LPS group and LPS+ MO group with 6 mice in each group. Mice in the control group were intraperitoneally injected with normal saline (30 mL/kg), mice in the MO group were intraperitoneally injected with MO (30 mg/kg), mice in the lipopolysaccharide group were intraperitoneally injected with lipopolysaccharide (10 mg/kg), mice in the lipopolysaccharide + MO group were intraperitoneally injected with MO (30 mg/kg), and the other side was injected with lipopolysaccharide (10 mg/kg) 30 min later. After 12 h, the mice were sacrificed for sampling and pathology and molecular biological tests were carried out. Cell experiment THP-1 cells in good condition were cultured in RPMI 1640 medium containing 10% fetal bovine serum for 24 h, and then induced to differentiate into macrophages with 100 ng/mL PMA. The control group, MO group, LPS group and LPS + MO group were established. After drug stimulation, the cell suspension of each group was collected, and the cells and culture medium supernatants were used for subsequent detectionResults:Compared with the control group, the injury degree of the lipopolysaccharide group was obvious, the alveolar cavity structure was destroyed, the inflammatory cell infiltration was increased, and the alveolar septum was obviously thickened in the tissue sections. After MO intervention, the injury degree of lung tissue injury was greatly improved, and MPO and the lung wet/dry weight ratio were also significantly decreased. The mRNA levels of the inflammatory cytokines IL-1β, IL-6 and TNF- α in lung tissues were also significantly decreased under MO intervention [(2.96±0.10) vs. (5.53±0.14), (8.62±0.17) vs. (12.31±0.09), (3.01±0.09) vs. (4.85±0.36)]. The expression levels of NLRP3, caspase-1 p20, GSDMD-N and ASC in the lung tissues of mice in the lipopolysaccharide group were significantly higher than those in the control group, while the phosphorylation level of AMPK in the lipopolysaccharide + MO group was increased, and the expression of scorched death-related proteins was effectively inhibited [(0.58±0.09) vs. (0.89±0.15), (0.19±0.08) vs. (0.93±0.16), (0.65±0.09) vs. (0.86±0.14), (0.30±0.12) vs. (0.47±0.10), all P<0.05]. At the same time, the secretion of the inflammatory factors IL-1β and IL-18, the main markers of scorch death in the tissue measured by ELISA, could also be alleviated by MO. In the cell experiment, MO also promoted the phosphorylation of AMPK, inhibited the expression of proteins related to NLRP3 inflammatory bodies, and significantly improved cell viability. Conclusions:MO attenuates LPS-induced acute lung injury by inhibiting NLRP3-mediated cell pyrogenesis by promoting the phosphorylation of AMPK.